The major objective of the proposed research is to determine the role of the human plasma enzyme, lecithin: cholesterol acyltransferase (LCAT) in normal and abnormal lipoprotein metabolism. First, the LCAT enzyme will be isolated and physico-chemically characterized. Second, the effects of the chemically defined phospholipids and specific apolipoproteins and apolipoprotein fragments on the activity of the purified LCAT will be examined. Third, the effect of LCAT on peripheral cell cholesterol homeostasis and lipoprotein cell interaction will be assessed through studies with pure cultures of human smooth muscle cells and skin fibroblasts. Fourth, a sensitive and specific radioimmunoassay for the LCAT enzyme will be developed. Fifth, levels of LCAT enzyme will be measured by radioimmunoassay and its catalytic activity measured by bioassay in normal subjects and in those with abnormalities of lipid metabolism, basally, and in response to dietary and pharmacological perturbation.